Idiopathic myelofibrosis a Philadelphia-negative chronic myeloproliferative disorder. Potentially curative therapies, such as stem-cell transplantation, are reserved only for a minority of patients. Currently palliative therapies such as androgen and hydroxycarbamide are commonly used but with poor results. Thalidomide has anti-angiogenic effect and also can inhibit cytokines, and therefore plays a certain role in the treatment of a subset of idiopathic myelofibrosis.
Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Primary Myelofibrosis ; drug therapy ; Thalidomide ; adverse effects ; therapeutic use ; Treatment Outcome

BACKGROUNDLenalidomide has emerged as an important treatment for patients with multiple myeloma (MM). However, its role in the management of MM is still controversial and requires further clarification. The aim of this study was to evaluate efficacy and safety of lenalidomide for MM using a meta-analysis.

METHODSWe searched the electronic databases including: PubMed, EMBASE and the Cochrane Center Register of Controlled Trials. Seven randomized clinical trials were identified, which included a total of 2357 patients with MM who received lenalidomide-containing, noncontaining lenalidomide regimens or placebo as induction therapy or maintenance therapy. The outcomes included overall response (OR) rate, complete response (CR) rate, 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, and different types of treatment-related adverse events. We calculated the risk ratios (RRs) as well as their 95% confidence intervals of these outcomes and pooled the results using RevMan 5.2 software.

RESULTSFor patients with previously untreated MM, OR rate and CR rate was significantly higher in lenalidomide-containing group than the control group. For relapsed or refractory MM patients, lenalidomide-containing regimens significantly improved the OR rate, CR rate, 3-year PFS rate and 3-year OS rate. With regard to MM patients after autologous stem cell transplantation, lenalidomide maintenance therapy significantly improved 3-year PFS rate but did not result in improved 3-year OS rate. In terms of toxicities, lenalidomide therapy has a higher rate of Grade 3-4 grade cytopenias, infection, deep-vein thrombosis, and diarrhea. Furthermore, the incidence of second primary malignancies was significantly higher in the lenalidomide group.

CONCLUSIONSThe lenalidomide-containing regimens as induction therapy clearly increased response rates and improved intervals of survival with acceptable toxicity rates for patients with MM. However, when physicians choose to use the lenalidomide as maintenance therapy, whether the benefits outweigh the risks should be taken into account.

Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Humans ; Multiple Myeloma ; drug therapy ; Randomized Controlled Trials as Topic ; Thalidomide ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome

In recent years, the incidence of chronic lymphocytic leukemia (CLL) is increasing. Microenvironment and immune system play a key role in the pathogenesis of CLL. The immune system is aggravated by the use of chemotherapeutic agents, such as fludarabine and cyclophosphamide with rituximab(FCR) which are the current standards in frontline therapy. This leads to an increase of infection incidence in patients, resulting in a poor prognosis. The present situation was changed by lenalidomide. Recent studies indicated that lenalidomide monotherapy in treatment of refractory or relapsed CLL patients, the overall response rate(ORR) reached about 32%-47%, CR roughly was 7%-13%; when lenalidomide and rituximab were combined for treatment of refractory or relapsed CLL patients, the ORR reached about 53%-66%, CR about 12%-13%. Moreover, when lenalidomide and ofatumumab were combined, the efficacy is improved significantly and the adverse reactions are greatly reduced. The adverse reactions are neutrophilic granulocytopenia, thrombocytopenia, anemia, tumor lysis syndrome(TLS), tumor flare reaction(TFR) and venous thromboembolism(VTE). This review focuses on the related studies and the latest progress about lenalidomide in CLL.
Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Thalidomide ; adverse effects ; analogs & derivatives ; therapeutic use

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of bisphosphonates (BPs) or other targeted agent therapies. MRONJ appears as exposed bone, pus, and swelling in the oral and maxillofacial regions. However, neither surgery nor conservative therapy can eliminate symptoms thoroughly. In addition to BPs, several antiresorptive and antiangiogenic agents, such as denosumab and bevacizumab, as well as targeted agents, such as sunitinib and temsirolimus, can cause osteonecrosis of  the  jaw according to the literature. This review aims to summarize the research progress on these new drugs.
Angiogenesis Inhibitors ; therapeutic use ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; drug therapy ; Bone Density Conservation Agents ; adverse effects ; Denosumab ; therapeutic use ; Diphosphonates ; Humans

PURPOSE: To report a case of retinal detachment with a macular hole following photodynamic therapy (PDT) using verteporfin and intravtreal bevacizumab injection in the treatment of myopic choroidal neovasclarization (CNV). METHODS: A 58 -year-old woman was diagnosed with myopic CNV and treated with a combination of PDT with verteporfin and intravitreal bevacizumab injection that same day. She received the second injection of intravitreal bevacizumab four weeks after the initial treatment. RESULTS: The patient developed a sudden decline in vision one week after the second injection; and was subsequently diagnosed with retinal detachment associated with a macular hole. She underwent standard three-port pars plana vitrectomy with internal limiting membrane peeling, fluid-air exchange and silicone oil injection. The retina was still firmly attached at the patient's final follow-up visit. CONCLUSIONS: PDT and intravitreal bevacizumab injection used for the treatment of myopic CNV can be associated with retinal detachment with a macular hole. Patients need to be informed about this potential complication, and a higher index of suspicion may be warranted in patients who report sudden vision loss after the treatment.
Angiogenesis Inhibitors/administration & dosage/*adverse effects/therapeutic use ; Antibodies, Monoclonal/administration & dosage/*adverse effects/therapeutic use ; Choroidal Neovascularization/*drug therapy ; Female ; Humans ; Injections ; Middle Aged ; Photochemotherapy/*adverse effects ; Retinal Detachment/*etiology ; Retinal Perforations/*etiology ; Vitreous Body

BACKGROUNDbevacizumab is a humanized recombinant vascular endothelial growth factor (VEGF) monoclonal antibody, which specifically binds to VEGF and inhibits tumor cell growth, proliferation and metastasis. We aimed to investigate the safety and pharmacokinetics of bevacizumab in Chinese patients with advanced cancer.

METHODSThirty-nine Chinese patients with metastatic or relapsed cancers who failed prior therapy were enrolled in this phase I study of bevacizumab. Bevacizumab was infused by a calculated pump at doses from 5 mg/kg to 15 mg/kg in 90 minutes. Patients underwent serial pharmacokinetic evaluations. Patients that received at least one infusion of bevacizumab were included in the safety study.

RESULTSThirty-five patients finished all 5 infusions following protocol. One patient withdrew after 3 infusions due to grade 3 proteinuria. Common adverse events possibly related to the study drug were proteinuria (17/39, 43.6%), hypertension (13/39, 33.3%), gingival bleeding (7/39, 17.9%), epistaxis (6/39, 15.4%), pharyngeal inflammation (6/39, 15.4%), fatigue (6/39, 15.4%) and stomatitis (4/39, 10.3%). Bevacizumab pharmacokinetics was linear within the range of 5 mg/kg q2w--10 mg/kg q2w and 15 mg/kg q3w. CL (clearance), Vd (volume of distribution at elimination) and Vss (volume of distribution at steady state) were similar after single and multiple doses at 5, 10 and 15 mg/kg.

CONCLUSIONSBevacizumab is well tolerated in Chinese patients. No unexpected adverse events were observed. There is no racial difference in the pharmacokinetics.

Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Asian Continental Ancestry Group ; Bevacizumab ; Female ; Humans ; Male ; Middle Aged ; Neoplasms ; drug therapy

Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Antibodies, Monoclonal ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Aspirin ; administration & dosage ; therapeutic use ; Bevacizumab ; Hemorrhage ; chemically induced ; Humans ; Hypertension ; chemically induced ; drug therapy ; Intestinal Perforation ; chemically induced ; surgery ; Neoplasms ; drug therapy ; Proteinuria ; chemically induced ; Thromboembolism ; chemically induced ; drug therapy

OBJECTIVETo assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer (mCRC).

METHODSSeventy-seven mCRC patients received BEV plus 5-Fu type, oxaliplatin or irinotecan-based chemotherapy. The clinical efficacy and bevacizumab-related adverse reactions were observed. The efficacy assessment was conducted after at least 2 cycles of BEV therapy. The adverse reactions were recorded in each therapy cycle. Among the 77 cases, 64 patients had finished the efficacy assessment. The adverse reactions in all patients were assessed.

RESULTSThe overall response rate (ORR) of BEV plus chemotherapy regimen was 18.75% (12/64), and the disease control rate (DCR) was 75.0% (48/64). In 27 patients who received the regimen as first-line treatment, the ORR reached 37.0% (10/27), while the DCR was 85.2%. Four patients with potentially resectable lesions became resectable after the regimen and received R0 resection of the liver metastases successfully. Twenty-five patients who received the regimen as second line therapy had poor result with ORR 8.0% and DCR 76.0%. Hypertension was observed in 12 cases, with 8 cases of grade 1, 3 cases of grade 2, 1 case of grade 3. Various bleedings occurred in 24/77 cases (31.2%), all were of grade 1-2, including 17 cases of epistaxis, grade 1 hemorrhoid bleeding in one case, hematuria in 3 case (2 of grade 1, 1 of grade 2), GI bleeding in 2 cases, hemoptysis in 1 case (grade 2), and proteinuria in 4 cases (grade 1). Intestinal perforation occurred in 1 case (0.3%). In two patients who had incomplete intestinal obstruction history appeared exacerbated intestinal obstruction symptoms after the application of BEV plus CPT11 regimen.

CONCLUSIONSBEV plus chemotherapy regimen as first-line treatment can improve the ORR and DCR of mCRC patients. When it was used as second- or later-line therapy, it may display satisfied DCR, although with a poor efficacy. The bevacizumab-related toxicity is mild and can be well tolerated.

Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bevacizumab ; Camptothecin ; adverse effects ; analogs & derivatives ; therapeutic use ; Colonic Neoplasms ; drug therapy ; pathology ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil ; adverse effects ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Hemorrhage ; chemically induced ; Humans ; Hypertension ; chemically induced ; Leucovorin ; adverse effects ; therapeutic use ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Proteinuria ; chemically induced ; Rectal Neoplasms ; drug therapy ; pathology ; Remission Induction ; Young Adult

This paper reports a case of pegylated interferon-associated retinopathy in a patient with chronic hepatitis C. A 32-year-old female with chronic hepatitis C undergoing pegylated interferon and ribavirin combination therapy complained of visual blurring. Features of interferon-associated retinopathy, including ocular complications such as cotton wool spots, retinal hemorrhages, macular edema, and branch retinal vein occlusion, were found in the fundus of both of her eyes. Pegylated interferon combination therapy was stopped, and the retinopathy of the patient was treated with intravitreal bevacizumab injections and panretinal photocoagulations. This case shows that pharmacokinetically improved pegylated interferon has ocular complications for patients with chronic hepatitis C. Accordingly, patients undergoing pegylated interferon treatment for hepatitis C need regular eye examinations for protection of their vision.
Adult ; Angiogenesis Inhibitors/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antiviral Agents/*adverse effects ; Female ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon-alpha/*adverse effects ; Polyethylene Glycols/*adverse effects ; Recombinant Proteins/adverse effects ; Retinitis/*chemically induced/drug therapy ; Severity of Illness Index

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.
Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asian Continental Ancestry Group ; Bevacizumab ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Humans ; Leucovorin ; administration & dosage ; adverse effects ; Male ; Middle Aged ; Neoplasm Metastasis ; Neutropenia ; chemically induced ; Prospective Studies ; Survival Rate ; Young Adult